As an aqueous gel, for example, sodium polyacrylate obtained by carrying out the polymerization of sodium acrylate and a crosslinkable monomer has been used in, a paper diaper, a gelling agent used in cosmetics, an electrolyte gelling agent used in a lithium battery, and the like. This sodium polyacrylate has an advantage such that the sodium polyacrylate forms a gel having a high viscosity only by the addition in a small amount, due to the repulsion between carboxylic acid ions (—COO-ions) possessed by the polymer and its crosslinking structure. However, when a salt such as sodium chloride which nullifies the repulsion between the above-mentioned carboxylic acid ions (—COO-ions) exists in a gel, repulsion between ions becomes smaller. Therefore, there is a possibility that an aqueous gel made of this sodium polyacrylate itself disintegrates (see, for example, Non-patent Literature 1).
Also, as a cationic thickener, there has been proposed a cationic thickener prepared by carrying out the polymerization of an amine-containing (meth)acrylic monomer, a vinyl monomer, a (meth)acryloyl group-containing monomer and a crosslinkable vinyl monomer (see, for example, Patent Literature 1). When this cationic thickener is used in a small amount, an aqueous gel having a high viscosity can be prepared. However, there is a possibility that this resulting aqueous gel disintegrates when a salt such a sodium chloride exists in the gel, as well as the above-mentioned sodium polyacrylate.
As an aqueous gel which hardly disintegrates even when a salt exists in the gel, there have been known a highly adhesive hydrogel composition prepared by carrying out the polymerization of 2-acrylamido-2-methylpropanesulfonic acid or its salt and a crosslinkable monomer in a polyhydric alcohol and an aqueous medium (see, for example, Patent Literature 2), a gel prepared by using neutralized crosslinkable poly(2-acrylamido-2-methylpropanesulfonic acid) and a gelling agent containing an oxidizing agent (see, for example, Patent Literature 3), and the like. However, the above-mentioned highly adhesive hydrogel composition and the above-mentioned gel do not simultaneously satisfy both of flexibility and mechanical strength.
As a polymer gel which is excellent in mechanical strength, there has been proposed a polymer gel having an interpenetrating network structure made of a physical crosslinking network structure formed by physical crosslinking, a first network structure formed by carrying out the polymerization of a first monomer and crosslinking the resulting polymer, and a second network structure formed by carrying out the polymerization of a second monomer and crosslinking the resulting polymer (see, for example, Patent Literature 4). However, this polymer gel has a defect such that its gel strength is lowered when the polymer gel is charged with positive electric charges.
Also, there have been carried out various attempts for repairing damaged tissues and the like. For example, there have been carried out some attempts such as the use of graft cells such as fetal myocardial cells, skeletal myoblasts or ES cells (embryonic stem cells), in order to repair myocardial tissues damaged by an ischemic cardiac disease such as angina pectoris or cardiac infarction. However, when the graft cells are administered to a tissue in the state of suspension of cells, the injection efficiency of the graft cells is low, and there is a possibility that a recipient tissue is damaged by puncture. Moreover, it has been pointed out that is it difficult that the tissue is repaired in a large area.
Therefore, in recent years, there have been developed a cell structure formed by using a scaffold and a cell sheet produced by molding cells into a sheet. It has been examined that this cell sheet is used as, for example, a cultured epidermal sheet for skin damage due to burn, a corneal epithelial cell sheet for cornea damage, an oral mucous cell sheet used after the excision of esophageal cancer with an endoscope, and the like.
A cell sheet is generally formed on a culture substrate and cells are cultured on the cell sheet. It is necessary that the cell sheet is isolated from the culture substrate when the cell sheet is actually used in treatment. As a process for isolating the cell sheet from the culture substrate, there have been known, for example, a process for isolating the cell sheet from the culture substrate by using a protease such as trypsin, a process for mechanically removing the cell sheet from the culture substrate by using a scraper, a pipette or the like, and the like.
However, according to these methods, when the cell sheet is isolated from the culture substrate, the cell sheet is damaged, or the survival rate of cells is lowered. Therefore, there has been investigated a means which can easily isolate the cell sheet from the culture substrate by improving the material of the culture substrate and its structure. For example, N-isopropylacrylamide (hereinafter, referred to as NIPAM) which is a temperature-responsive polymer has properties such that NIPAM is swollen and becomes liquid at low temperatures, and that its phase transition occurs, and NIPAM is quickly shrunk and gelated at a temperature of around 34° C. Therefore, it has been proposed that cells are cultured on NIPAM which has been gelated at a temperature of 37° C., and the cells which are cultured on the gelated NIPAM are superposed on the other cells which are cultured on the gelated NIPAM, and thereafter, a culture temperature is lowered to 34° C. or lower, to remove NIPAM, and directly superpose the cells (see, for example, Non-patent Literatures 2 to 4). However, since NIPAM is not sufficient in biocompatibility, there is a possibility such that the secretion of an inflammatory protein is accelerated by the adhesion of macrophages to NIPAM during the culturing of cells, and thereby an immunological rejection reaction is caused when NIPAM is applied to a patient.
As a cell culture support, there has been proposed a cell culture support having plural convex portions each of which has a top face and plural concave portions between the plural convex portions, in which the opening of the above-mentioned concave portions has a size to which cells to be cultured cannot be entered, and the above-mentioned cell sheet is removable (see, for example, Patent Literature 5). However, this cell culture support has some defects such that the cell culture support is not suite for producing in a large scale, and that the cell culture support is not inexpensive, as well as the cell culture support is not sufficient in biocompatibility. Therefore, the secretion of an inflammatory protein is accelerated by the adhesion of macrophages to the cell culture support during culturing, and thereby there is a possibility that immunological rejection reaction is generated when the cells are applied to a patient.
As a medical material having a small interaction with biological components such as proteins and hemocytes, and being excellent in biocompatibility, there has been proposed a medical material which is produced by forming a polymer obtained by carrying out the polymerization of a monomer composition containing N-methacryloyloxyethyl-N, N-dimethylammonium-α-N-methylcarboxybetaine on the surface of a substrate (see, for example, Patent Literature 6). It is considered that cells such as macrophages would not be easily adhered to the medical material, because the amount of cells to be adhered is small. However, since the flexibility of its surface is small, there is a possibility that cells will be damaged when the cells which are grown up on the surface of the medical material are removed from the medical material.